In spite of the worldwide effort, the human immunodeficiency virus (HIV) has until now defeated all attempts to develop an effective anti-AIDS drug or vaccine by resorting to hypermutation tactics. Mutation tactics have likewise until now hampered attempts to develop effective vaccines to other RNA-virus caused diseases such as leukemia and influenza.
One of the strategies for combating RNA-viruses such as the HIV AIDS (acquired immunodeficiency syndrome) virus is to inactivate the reverse transcriptase of HIV (HIV RT). Unfortunately, the unusually high mutation rate of the virus has hitherto prevented the development of an effective anti-HIV drug or vaccine. The hypermutable HIV can develop resistance rapidly toward all known inhibitors of small molecular weight (M.sub.r &lt;1000 dalton) such as AZT, ddC, ddI and nevirapine [Larder, et al., Science 243, 1731 (1989); Larder and Kemp, Science 246, 1155 (1989); St. Clair, et al., Science 253, 1557 (1991); Shih, et al., Proc. Natl. Acad. Sci. USA 88, 9878 (1991)].
It is known (Chuan and Wang, J. Biol. Chem. 263, 13003 (1981)) that the affinity reagents 3'-O-(5-fluoro-2,4-dinitrophenyl) ADP ether and 3'-O-(5-fluoro-2,4-dinitrophenyl) ATP ether are capable of labelling the active site of mitochondrial F.sub.1 -ATPase and of inhibiting the ATPase. However, 3'-O-(5-fluoro-2,4-dinitrophenyl) ADP ether and the corresponding ATP ether require a million-fold higher molar concentration to inhibit the reverse transcriptase of HIV (HIV RT), nor can they inhibit HIV RT or other RNA-viruses in a manner which is mutation-insensitive.
It is also known (Fukui and De Clercq, Biochem J 203, 755-760 and Shannon, Ann. N.Y. Acad. Sci. 284, 472-507) that anti-viral compounds such as poly(2-fluoroadenylic acid), poly(2-bromoadenylic acid), poly(2-iodoadenylic acid) and 1-(4-fluorobenzyloxy) adenosine polyadenylic acid, inhibit reverse transcriptase. All of these compounds are derivatized by attaching halogen atoms or other groups to the adenine residues in the polymers. The best of these compounds is (fl.sup.2 A).sub.n which inhibited murine leukemia RT with an IC.sub.50 of 0.04 .mu.g/ml. The FDNP-poly[A] of the present invention inhibited the same RT with an IC.sub.50 of 0.0017 .mu.g/ml (at a 23-fold lower concentration).